DE60223930T2 - ANTIBACTERIAL WOUND ASSOCIATION - Google Patents

Abstract

An antibacterial wound dressing is based on or derived from gel-forming fibres such as carboxymethyl cellulose or alginate fibres having silver ions linked thereto at some but not all of the exchangeable sites such that the distribution of silver ions over the exchangeable sites is substantially uniform. The silvered fibres for the wound dressing can be prepared by contacting an assembly of precursor gel-forming fibres having exchangeable sites under conditions which do not cause irreversible gelling of the fibres with an amount of a solution containing silver ions so as to link silver ions at some but not all of the exchangeable sites, the whole of the assembly of precursor gel-forming fibres being contacted essentially simultaneously with the entire solution containing silver ions.

Description

Field of the invention

The The present invention relates to wound dressings, in particular an antibacterial Wound dressing based on silver-plated gel-forming fibers, and an improved method for the manufacture of such a wound dressing.

Background of the invention

It has been known for many years that silver is a useful broad-spectrum antibacterial agent paired with fabric compatibility, and there have been many proposals to incorporate silver into wound dressings to take advantage of the bactericidal properties of silver in a wound dressing. In addition, silver has previously been applied to fibrous material for non-wound dressing purposes, usually for the purpose of increasing electrical conductivity, see, for example UK-A-927.115 . WO-A-92/16589 . DE-C-2,639,287 . US-A-5,302,415 . US-A-5,186,984 . US-A-4,752,536 . US-A-4,643,918 . JP-010207473A and JP-020153076 , Silver has been variously applied in these references to such fibers, which are generally non-gelling, some of which involve the immersion of the fibers in a silver solution, but details of the procedures used are often lacking.

Carboxymethyl cellulose, especially carboxymethylated lyocell, has the ability to absorb a large amount of water and to form a gel on its surface. It has been found that this property of the material is particularly advantageous in the formation of wound dressings which are both absorbent and gel-forming. The carboxymethylation of cellulose is in WO-A-93/12275 and the use of carboxymethylcellulose for wound dressings is described in US Pat WO 94/16746 described. Calcium (or sodium / calcium) alginate is another material that is useful in the formation of wound dressings because of its absorbency and gelling ability.

Gel-forming fibers for use in wound dressings are water-absorbent fibers that become moist and slippery or gelatinous upon ingestion of wound exudate, thus reducing the tendency for the surrounding fibers to adhere to the wound. The gel-forming fibers can also swell. Gel-forming fibers may be of the type which retains its structural integrity upon absorption of exudate, or may be of the type which upon absorption of exudate loses its fibrous shape and becomes a structureless gel or solution. GB-A-1,328,088 . WO-A-91/11206 . WO-A-92/22285 . JP-A-4146218 and WO-A-02/36866 disclose the incorporation of silver into calcium sodium alginate, WO-A-01/24839 discloses silver chloride-containing carboxymethylcellulose fibers and WO-A-02/43743 discloses the incorporation of silver into a polymer, which may be carboxymethyl cellulose or an alginate.

It However, there were special problems associated with the use of Silver in wound dressings, due to the fact that silver compounds are photosensitive and darken when exposed to light. This can be for the production lead products, which have an unattractive visual appearance, even if they are technically suitable for use as wound dressings.

It There are three specific aspects of the darkening of the silver compound in light, which one must turn to, if one makes an effort, one produce commercially acceptable silvered wound dressing. One Aspect is the actual color of the product, namely the need to use a product To have color for the consumer is acceptable. The second aspect is the need a product with a uniform appearance manufacture. The third aspect is stability (shelf life) the color of the dressing inside, whatever packaging is used to package the dressing. When fibers are mixed and both fibers are white, will any imperfection in the mixture from the consumer not noticed. Although this is primarily a visual problem, could Extreme of streaks or discoloration within a wound dressing an indication of incomplete or inappropriate silver additions to the wound dressing or parts from him or even the presence of excessive amounts of silver in some Be areas that indicate potential problems in use could. Silver as an antibacterial material should be in metered dosages be used and this would not be the case when the amount of silver from bandage to bandage changed.

Beech kettles are known for use in fiber treatment processes; For example, it is known that cellulose fiber can be dyed by placing it in a cauldron and pumping the dye liquor through the cauldron to give a product having a uniformly colored appearance. A cauldron is a sealed container with inlets and outlets; it is capable of being pressurized and heated when required, and is placed in a circuit so that liquid can be pumped through the sump. In the container is a porous basket in the form of a stainless steel net, and the product to be treated is evenly packed in the net to be pumped during the pumping process ensure uniform and uniform flow of fluid through the network.

Attempts have therefore been made by the Applicant to apply the silver to carboxymethylcellulose fiber in a cauldron just as if the carboxymethylcellulose were dyed with a dye by adding a solution of a silver-containing compound (denatured industrial alcohol (IMS), H ₂ O + AgNO ₃ ) the Beuchkessel is used. The silver-containing liquid was pumped from the center towards the periphery. In this method, a basket containing 1.25 kg of the carboxymethylcellulose fiber was placed in the cauldron before the cauldron was filled with liquid. Then, 10.4 liters of a solution of (IMS, H ₂ O + AgNO ₃ ) prepared from 6.4 L of IMS, 4.0 L of water, 25 g of AgNO ₃ , with a silver concentration of 0.240 w / v. and a temperature of 30 ° C pumped through the Beuchkessel, which had a capacity of about 12 liters. After the liquid had been pumped in a circle for 30 minutes, the liquid was run out of the fiber and the product was immediately fed to subsequent stages, which included the application of a textile finish and drying. After all subsequent treatments had taken place, the fiber was removed and exposed to light. It was found that the fiber was not uniform in its silver uptake. It was found that the product produced by this process was very streaky.

It Therefore, attempts have been made to change the cupping method by: a basket with upward flow was used, which is the liquid from below rather than from the center. It was found that such a procedure improves the product in the sense that it was less streaky, but there was a marked gradation of Silver pickup from the ground to the top of the basket.

It It is an object of the present invention to provide an antibacterial Wound dressing, based on or derived from silver-plated gel-forming Fibers provide, in which reduces the above disadvantages are or are essentially eliminated. It is another task of the present invention, silvered fibers for an antibacterial wound dressing, based on silver-plated gel-forming fibers, in which the above disadvantages are reduced or substantially eliminated are eliminated.

Disclosure of the invention

We have found that better wound dressings are made of silver-plated gel-forming Fibers can be obtained which are more capable of accepting silver ions than Silver ions are available in the solution used for silvering, so that in the working step of silvering does not absorb all the silver ions by: the silver ions that are taken up are substantially uniform over the Bodies are distributed that are capable to record it.

Antibacterial wound dressings according to the invention so do some of gel-forming fibers with it, but not All silver ions bonded to all exchange sites are and are characterized in that the distribution of silver ions over the Substitution sites is substantially uniform.

Usually will only a minority of the sites capable of ion exchange with silver ions on the gel-forming fibers in making the wound dressings of the Invention in fact silvered, and common will not exceed 20%, often not more than 10% of such Spots silvered.

We have also found that better silvered fibers for wound dressings get can be when bringing the gel-forming fibers into contact with each other with silver ions capable Replacement points for silvering the fibers with the solution to Silvering is carried out in such a way that the whole solution for silvering substantially simultaneously with the entire amount of gel-forming fibers is brought into contact with the wound dressing rather than being gradual or partially brought into contact.

• (i) Bilden einer Anordnung von gelbildenden Faservorläufern, mit zum Austausch mit Silberionen fähigen Austauschstellen darauf, um Silberionen an die Fasern zu binden, und
• (ii) In-Kontakt-Bringen der Anordnung von gelbildenden Faservorläufern mit einer Silberionen enthaltenden Lösung unter Bedingungen, welche kein irreversibles Gelieren der Fasern bewirken, um dadurch Silberionen an die Fasern an Austauschstellen zu binden,

und ist dadurch gekennzeichnet, dass die gesamte Anordnung von gelbildenden Faservorläufern zur Bildung des Wundverbands im Wesentlichen gleichzeitig mit der gesamten Silberionen enthaltenden Lösung in Kontakt gebracht wird, die Silberionen enthaltende Lösung in einer solchen Menge verwendet wird, dass nur genügend Silberionen vorhanden sind, um an einige, aber nicht alle Austauschstellen auf den gelbildenden Faservorläufern zu binden.According to the invention, therefore, a process for producing silver-plated fibers for antibacterial wound dressings based on silver-plated gel-forming fibers comprises the steps:

• (i) forming an array of gel-forming fiber precursors having exchange sites thereon for exchange with silver ions for binding silver ions to the fibers, and
• (ii) contacting the array of gel-forming precursor fibers with a solution containing silver ions under conditions which do not cause irreversible gelling of the fibers to thereby bind silver ions to the fibers at exchange sites;

and characterized in that the entire array of gel-forming fiber precursors for forming the wound dressing is contacted substantially simultaneously with the entire silver ion-containing solution, the silver ion-containing solution being used in an amount such that only enough silver ions are present to to tie some, but not all, replacement sites on the gel-forming fiber precursors.

The Essentially simultaneous contacting can be done as a batch process be achieved by the gel-forming fibers quickly into the silver-containing solution be submerged and submerged to form the wound dressing.

• (i) Bilden von Faservorläufern mit zum Innenaustausch mit Silberionen fähigen Stellen darauf, um ein versilbertes Seil zu bilden, und
• (ii) Versilbern der Fasern unter Verwendung einer silberhaltigen Lösung, welche kein irreversibles Gelieren der Fasern bewirkt,

dadurch gekennzeichnet, dass, um eine gleichmäßige Aufnahme von Silber zu ergeben, die Fasern in die Silberlösung eingetunkt werden, indem die Fasern direkt in die Lösung herabgelassen werden und die Fasern sofort unter die Oberfläche der Lösung gestoßen werden. Die resultierenden versilberten Fasern können dann verarbeitet werden, zum Beispiel in herkömmlichen Schritten, um den Wundverband zu bilden.Thus, in one embodiment, the present invention provides a process for the preparation of an antibacterial wound dressing based on silver-plated gel-forming fibers, which comprises the following steps in sequence:

• (i) forming fiber precursors having silver ions ion-exchangeable sites thereon to form a silver-plated rope, and
• (ii) silvering the fibers using a silver-containing solution which does not cause irreversible gelling of the fibers,

characterized in that in order to give a uniform uptake of silver, the fibers are dotted into the silver solution by lowering the fibers directly into the solution and immediately pushing the fibers below the surface of the solution. The resulting silvered fibers can then be processed, for example, in conventional steps to form the wound dressing.

gelling Fibers suitable for use in wound dressings tend to be extremely reactive to silver ions to be, that is, the Silver ions bind very fast and very strongly to the ion exchange sites on the fibers. We have found that it is applied unlike dye molecules in a Beuchkessel, after initial Binding essentially no redistribution of silver ions. This means that when such fibers are in contact slowly or gradually brought with a solution containing a limited amount of silver ions are the proportions of fibers that are first in contact with silver solution come, relatively large Absorb quantities of silver ions, so that those portions of the fibers, the last come in contact with silver-containing solution, almost at all can not have silver. The resulting fibers have no uniform coloring at the beginning and to dye dark in different degrees. It would not be possible, this disadvantage to overcome by a larger amount used by silver, because this leads to over-silvering of the shares the fibers that come in contact with the solution first, followed by Lack of uniformity of Silver distribution in the product could lead to or failure, to take advantage of the silver content of the solution with subsequent problems over the disposal of the waste water as well as the waste of valuable Silver.

It It is also important that the volume of the solution is adjusted so that essentially all shares of her substantially simultaneously come in contact with gel-forming fibers. If the volume of solution is great compared to the volume absorbed by the gel-forming fibers so that some portions of the solution are relatively distant Of all the fibers, silver ions in this part tend to be in Direction to the fibers they encounter first, to diffuse and with to interact with them and heavier deposit on these To give fibers, where the desired even distribution is impaired.

The Volume of solution, with which the gel-forming fiber precursors are brought into contact, is particularly preferably adjusted so that essentially the entire liquid through the solution the water-absorbing gel-forming fiber is taken, wherein essentially no free liquid left behind becomes. In such a situation, there are essentially none Waste solution which must be discarded at this stage.

The Time interval between the beginning of immersion of the gel-forming Fiber into the silver-containing solution and the time at which sufficient gel-forming fiber is around the To form wound dressing, completely submerged is desirably not more than 10 seconds, preferably 5 seconds or less. Practically, that is Time usually 2 to 3 seconds.

It was surprisingly found that by drowning the fiber in a casual Way into the solution a very uniform silver shot he follows. Furthermore, it has been found that it is desirable to use the amount of silver-containing solution to minimize to produce a silvered gel-forming fiber. The minimum volume of liquid, that needed to completely cover a given amount of gel-forming fiber, if the fiber is in the solution can be easily determined by an experiment. Once the minimum volume of liquid has been determined, this amount of silver-containing solution is produced, and the fiber just gets into the solution dotted so that the fiber picks up the solution, that is, it fill those solution in the container, in which it is located. This means that there is minimal superfluous solution and the amount of silver-containing solution being handled must, is also minimized.

The silver-containing solution is preferably in a container, which may be a closed container or an open container. The size of the container and therefore the volume of solution it contains and the amount of gel forming Fiber are correlated so that the entire volume of the solution comes into contact with the fibers substantially simultaneously.

The Gel-forming fiber is preferably a carboxymethylated cellulose (CMC) fiber. The lyocell-derived CMC generally has a degree of substitution from 0.1 to 0.5, preferably 0.2 to 0.4. This gives a sufficient Number of carboxylate groups that the gel-forming and absorbent Properties for The use as a wound dressing are appropriate, but without so high be that a substantial portion of the fiber becomes soluble. The CMC can by Cellulose, preferably from lyocell, derived by carboxymethylation become. An alternative fiber is calcium or sodium / calcium alginate. The fiber brought into contact with the silver-forming solution is preferably dry, although with a liquid may be premoistened, which does not cause irreversible gelling. It is preferably in the form of a strand or rope, but can in another embodiment in staple fiber form (cut), e.g. B. in standard, conventional lengths, be. To fast fiber / solution contact to facilitate the fiber is preferably in relatively open, casual form as opposed to tightly packed, forced Form used. A strand of fiber, essentially a pretty loose bundle made of continuous rope or cut fibers, accomplishes this. It is preferred in commercial operation, the solution in Substantially simultaneously with enough fiber to bring into contact more than one wound dressing, for example 1000 to 10 000 bandages form. So can strands up to many meters in length, For example, 20 to 200 meters or more, can be used. The Fiber may have a soft finish.

Of the Silver content of the silvered fibers is generally of the order of magnitude from 0.01 to 10 wt .-%, more precisely 0.1 to 5 wt .-%, preferably 0.5 up to 2% by weight, stronger preferably 0.9 to 1.5 wt .-%. This allows good antibacterial activity to be achieved without toxicity problems. This is comparable to a theoretical maximum of the order of magnitude of 16% if all replacement sites on CMC lyocell with a degree of substitution are replaced by 0.3, and about 38% when all replacement points on conventional Alginate fiber are exchanged.

The Contacting is carried out so that irreversible gelling the fibers is avoided. It is preferred for the silver ions to be an aqueous one organic solution, especially a watery alcoholic Solution, as a mixture of ethyl alcohol and water.

The water content of such a solution generally does not exceed 50% by volume and is preferably from 25 to 50% by volume. The silver is provided in the form of a source of soluble silver ions, for example a soluble silver salt of an acid such as silver nitrate. Solubility in the required concentration in the solution to be used is essential, so that silver-containing substances such as ceramic ion exchange resins or other insoluble silver sources should not be used. Generally speaking, the silver content of the bath may be on the order of 0.1 to 1% w / v, preferably 0.25 to 0.5% w / v. A typical solution may comprise, for example, 2.7 l of IMS (denatured industrial alcohol), 1.8 l of water and 25 g of AgNO ₃ to a concentration of 0.35% w / v. To give silver.

It may be desirable be the fiber or the container while and / or immediately after the addition to stir or move to the To facilitate contact of the entire fiber with the entire solution.

If a continuous process is needed instead of a batch process, could the fiber in synchronism with the desired speed of feed of silver solution a pipe or a pipe can be lowered to the desired amount to give silver content on the gel-forming fiber.

If no further wet processing steps are needed before drying, the silvered fibers, suitably in the form of a rope, then expressed be, preferably at about 1,5-2 l remaining liquid per kg of rope. This expressing can be done manually be or can be mechanized, for example by the application from vacuum pressure or over a press. In another embodiment, the rope can run off be left and centrifuged. Because the binding of silver ions is very is done quickly, it is not necessary to contact the liquid from the contact the silvered fibers quickly or substantially simultaneously to remove, to a uniform silver deposit but in practice this can be done in the case that others undesirable Effects occur, be preferred.

It normally there is little silver remaining in the liquid being expressed, since practically everything has been implemented with the gel-forming fiber. This can be demonstrated by testing the liquid with NaCl solution is, with almost no precipitation is observed.

The resulting silver-plated rope of gel-forming fiber can then be processed into a wound dressing in a known manner, for example as in WO 94/16746 is disclosed.

Additional wet processing steps may be performed on the silvered fiber before drying. For example, a conventional textile finish may preferably be applied in a conventional amount (e.g., about 0.5% w / v) of an aqueous organic liquid (e.g., IMS / water) which does not cause irreversible gelling of the fiber , This may be preceded by a light stability-imparting treatment, for example a treatment as in WO 02/43743 which includes a metal halide such as sodium chloride.

The dried silver-plated fiber can then, if necessary Cut, typically 50mm staple lengths, to be processed To produce a nonwoven fabric, for example using a Textile carding and folding device. The tissue can then be treated to improve its strength, for example by needling, before it's needed Association sizes, for Example squares, typically 10 cm × 10 cm, are cut. The cut pieces can then packed, usually in individual bags, and in a conventional manner, for example be sterilized using gamma irradiation before they are ready to use.

The Results of the implementation this change are illustrated by the following examples.

EXAMPLE I

The above described cupping method and method according to the invention were carried out separately on carboxymethylated lyocell with a degree of substitution of about 0.3. The kettle process was carried out as described in the Background of the Invention The process of the invention was carried out using a solution comprising 2.7 liters of IMS, 1.8 liters of water and 25 grams of AgNO ₃ on a strand of carboxymethylated lyocell immersed and completely immersed in the solution over a period of about 5 seconds, so that the strand took up the solution and thus all parts of the solution were in contact with the carboxymethylated lyocell and essentially all of it was collected The silver-plated strand had an average silver content substantially the same as that of the strand treated by the Bechboiler process, and in each case the reacted rope was stretched lengthwise and allowed to dry, not in the dark, but exposed to the light Material made using the cauldron showed extremely different levels of gray or pi nk, with the majority of the rope, typically 75%, undyed. The material made by the process of the invention was mostly gray / pink colored with perhaps as little as about 5% to 10% undyed rope.

The Improvement was further illustrated when the rope in absentia dried and cut by daylight / opened / carded / needled and as a piece of tissue was investigated. If these tissues are exposed to intense daylight (eg 1000 × standard) for 30 Minutes were exposed, the material produced under Use of the Beuchkessels, mottling, whereas the material produced by the method of the invention, completely uniform in the Color was.

When another experiment, not according to the invention, The rope was made of fiber rather than stranded in about five seconds to be lowered, shimmying as a longitudinal feeder into the container Silver nitrate-containing solution guided. This meant that it was about fifteen Seconds took the rope down into the solution. After this the fiber had been dried, the rope was exposed to the light, to show the silver image visually, and side by side with the rope according to the invention as prepared above on a white table top designed. The rope, which was lowered in a longitudinal feeder, was over about the first 1/3 to 1/2 of its length dyed deep, and the end that went in last was very faintly colored and blotchy. The stranded rope was essentially along its length evenly colored.

EXAMPLE II

Two solutions of silver nitrate (1.58 g) in water (1 liter) were used in the laboratory at room temperature produced. Alginate rope (100g) was intentionally added to the first given slow way, d. h., it took about 30 seconds to fully submerge to reach. To the second was a similar amount of alginate rope given, but this time in less than 5 seconds.

Both Ropes were out of solution removed and after expressing excess fluid laid out on the daylight-exposed laboratory bench. Soon after, but more on the following day, a huge difference was evident visible, noticeable. The rope with slow submersion was dark (attributed to the discoloration, caused by silver pickup) at one end of the rope, but mostly unstained at the other end of the rope. The rope with fast submersion was along the full length discolored to a remarkably uniform extent.

In a production situation would the water-based solution be replaced with an IMS / water based solution to adhere the Filaments and gels caused by hydrogen bonding, if only water is used, avoid it.

Claims (20)

A process for producing silvered fibers for use in antibacterial wound dressings, comprising the steps of (i) forming an array of gel-forming fiber precursors having exchange sites thereon for exchange with silver ions for binding silver ions to the fiber, and (ii) contacting placing the gel-forming precursor fiber with a silver ion-containing solution under conditions which do not cause irreversible gelling of the fibers to thereby bind silver ions at some, but not all, exchange sites, characterized in that the entire array of gel-forming precursors is substantially simultaneous with the whole Silver ion-containing solution is used in such an amount that sufficient silver ions are present to bind to some, but not all, exchange sites on the gel-forming fiber precursors. Method according to claim 1, wherein the silver ion-containing solution is used in an amount so that will be enough Silver ions are present to not more than 20%, preferably 10% the replacement sites on the gel-forming fiber precursors tie. Method according to claim 1 or 2, in which the method is a batch process, wherein the Arrangement of gel-forming fiber precursors containing the silver ions solution gets in contact quickly and completely in the solution is dipped. Method according to claim 3, where the solution in a container is, and is a lot that is needed to gelforming fiber precursor Completely so that the fibers fill the solution in the container. Method according to claim 3 or 4, the time between the beginning of the immersion the arrangement of gel-forming fiber precursors around a wound dressing to form into the solution and the time at which the arrangement of gelbildenden fiber precursors to to form a wound dressing completely immersed in the solution, not more than 10 seconds. Method according to claim 5, wherein the time period is not more than 5 seconds. Method according to one the claims 3 to 6, wherein the einzonauchende arrangement of gelbildenden fiber precursors dry is. Method according to one the claims 4 to 7, wherein the solution containing silver ions in a closed container located. Method according to one the claims 4 to 7, wherein the solution containing silver ions in a open container located. Method according to one the claims 1 to 9, wherein the gel-forming fiber precursors in rope form or in staple fiber form is present. Method according to one the claims 1 to 10, wherein the arrangement of gel-forming fiber precursors in Form of a strand is present. Method according to one the claims 1 to 11, wherein the gel-forming fiber precursors carboxymethyl cellulose fibers are. Method according to claim 12, wherein the carboxymethylcellulose fiber is a carboxymethylated Lyocell fiber is. Method according to claim 13, wherein the carboxymethylated lyocell fiber has a degree of substitution from 0.2 to 0.4. Method according to one the claims 1-11 wherein the gel-forming fiber precursors are calcium alginate or sodium calcium alginate fibers are. Method according to one the claims 1-15, wherein the assembly processes silver-plated gel-forming fibers is going to wound dressings to build. Antibacterial wound dressing derived from gel-forming Fibers containing silver ions at some but not all exchange sites have bound, characterized in that the distribution of Silver ions over the replacement points are essentially uniform and the bandage is through the method of claim 1 obtainable is. Wound dressing according to claim 17, with the silver ions at not more than 20% of the exchange sites bound to the gel-forming fibers. Wound dressing according to claim 17 or 18, wherein the gel-forming fibers are carboxymethylated cellulose fibers are. Wound dressing according to claim 17 or 18 wherein the gel-forming fibers are calcium alginate or sodium / calcium alginate fibers are.